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BACKGROUND RESULTS CONCLUSION Histamine may lead to low blood pressure, skin flushing and edema when it accumulates in large amounts in the body. Therefore, establishing sensitive methods for the detection of histamine in foods is extremely important to ensure food safety and human health.The MI‐Cu‐GMP NPs (2‐methylimidazole‐copper‐guanosine monophosphate nanozymes) with high laccase‐like activity were synthesized. Using the prepared molecular imprinted membrane as biomimetic antibody and MI‐Cu‐GMP NPs as marker, a sensitive direct competitive biomimetic enzyme‐linked immunoassay (BELISA) method for rapid detection of the histamine in foods was developed. Under optimal conditions, the limit of detection (LOD, IC15) and sensitivity (IC50) of the BELISA method for histamine was 0.05 mg L−1 and 1.22 mg L−1, respectively. The liquor samples spiked with histamine was detected by the BELISA method with satisfactory recoveries ranging from 90.00% to 116.00%. Further, the level of histamine in three samples (cooking wine, rice vinegar and soy sauce) was tested by the BELISA and high‐performance liquid chromatography (HPLC), with no significant difference found between the two methods.Given the advantages, the established BELISA method is expected to provide practical guidance for the monitoring of histamine in food and provides a foundation for the detection of other food hazards. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Aims: This study investigated histamine intake and its associations with clinical and biochemical findings in patients with Behçet syndrome. Methods: Patients with Behçet syndrome were prospectively enrolled using a crosssectional, multicenter, and online survey design. Sociodemographic parameters, including age, gender, smoking and alcohol intake, nutritional counseling history, anthropometric measurements, clinical characteristics, and biochemical results, were obtained using an online questionnaire. Dietary histamine intake was determined using a food frequency questionnaire. Results: The study included 66 patients (mean age: 37.5±11.3 years, women: 53%. Food consumption was reported to trigger oral aphthae in 81% of the individuals, and the most frequently reported triggers were eggplant (37.5%), tomatoes (37.5%), and citrus fruits (34.3%). There was a significant positive correlation between dietary histamine intake and white blood cell counts (r=0.650; p=0.050). There were no significant differences in the clinical characteristics, including oral aphthae, genital ulcers, uveitis, dermatologic lesions, gastrointestinal system involvement, joint involvement, and vascular involvement between patients with low and high dietary histamine intake. A positive correlation was found between dietary histamine intake and the frequency of attacks (r=0.324; p=0.008). Conclusions: This study showed that increased dietary histamine intake was associated with an increased frequency of attacks in patients with Behçet syndrome. Oral aphthae are associated with certain foods, such as eggplant, tomatoes, and citrus fruit. [ABSTRACT FROM AUTHOR]

Mast cell–derived mediators induce vasodilatation and fluid extravasation, leading to cardiovascular failure in severe anaphylaxis. We previously revealed a synergistic interaction between the cytokine IL-4 and the mast cell–derived mediator histamine in modulating vascular endothelial (VE) dysfunction and severe anaphylaxis. The mechanism by which IL-4 exacerbates histamine-induced VE dysfunction and severe anaphylaxis is unknown. We sought to identify the IL-4–induced molecular processes regulating the amplification of histamine-induced VE barrier dysfunction and the severity of IgE-mediated anaphylactic reactions. RNA sequencing, Western blot, Ca2+ imaging, and barrier functional analyses were performed on the VE cell line (EA.hy926). Pharmacologic degraders (selective proteolysis-targeting chimera) and genetic (lentiviral short hairpin RNA) inhibitors were used to determine the roles of signal transducer and activator of transcription 3 (STAT3) and STAT6 in conjunction with in vivo model systems of histamine-induced hypovolemic shock. IL-4 enhancement of histamine-induced VE barrier dysfunction was associated with increased VE-cadherin degradation, intracellular calcium flux, and phosphorylated Src levels and required transcription and de novo protein synthesis. RNA sequencing analyses of IL-4–stimulated VE cells identified dysregulation of genes involved in cell proliferation, cell development, and cell growth, and transcription factor motif analyses revealed a significant enrichment of differential expressed genes with putative STAT3 and STAT6 motif. IL-4 stimulation in EA.hy926 cells induced both serine residue 727 and tyrosine residue 705 phosphorylation of STAT3. Genetic and pharmacologic ablation of VE STAT3 activity revealed a role for STAT3 in basal VE barrier function; however, IL-4 enhancement and histamine-induced VE barrier dysfunction was predominantly STAT3 independent. In contrast, IL-4 enhancement and histamine-induced VE barrier dysfunction was STAT6 dependent. Consistent with this finding, pharmacologic knockdown of STAT6 abrogated IL-4–mediated amplification of histamine-induced hypovolemia. These studies unveil a novel role of the IL-4/STAT6 signaling axis in the priming of VE cells predisposing to exacerbation of histamine-induced anaphylaxis. [ABSTRACT FROM AUTHOR]

Bioactive amines in foods are associated with beneficial health effects, but some can also cause food poisoning and intolerance. This study aimed to investigate the occurrence and levels of nine bioactive amines in ten conventional and non-conventional fruits and vegetables (seriguela, marolo, custard apple, acerola, jabuticaba, starfruit, kale, ora-pro-nobis, almeirão-roxo, and serralha) using HPLC-FL. Putrescine was the prevalent amine in custard apple, acerola, and ora-pro-nobis; whereas spermidine was predominant in jabuticaba, starfruit, and kale; and tyramine in seriguela and marolo. Tryptamine was not detected in any sample. Histamine was only detected in ora-pro-nobis, and serotonin only in starfruit. Total amine contents ranged from 3.24 to 58.83 mg/kg, with the lowest levels in serralha and the highest in seriguela. The median contents of spermidine varied from 1.32 to 13.42 mg/kg, with the lowest levels in serralha and the highest in seriguela. The highest agmatine levels were found in acerola, starfruit and serralha. Based on the levels of amines, seriguela, marolo, custard apple, acerola, jabuticaba, and kale could be dietary sources of the polyamine spermidine; and starfruit a source of serotonin. However, individuals using monoamine-oxidase inhibitor drugs should limit the consumption of seriguela and marolo, due to the high tyramine levels, to avoid adverse effects. In a similar way, individuals with histamine intolerance should avoid the consumption of ora-pro-nobis. [ABSTRACT FROM AUTHOR]

The majority of somatosensory DRG neurons express GABAA receptors (GABAAR) and depolarise in response to its activation based on the high intracellular chloride concentration maintained by the Na-K-Cl cotransporter type 1 (NKCC1). The translation of this response to peripheral nerve terminals in people is so far unclear. We show here that GABA (EC50 = 16.67μM) acting via GABAAR produces an influx of extracellular calcium in approximately 20% (336/1720) of isolated mouse DRG neurons. In contrast, upon injection into forearm skin of healthy volunteers GABA (1mM, 100μl) did not induce any overt sensations nor a specific flare response and did not sensitize C-nociceptors to slow depolarizing electrical sinusoidal stimuli. Block of the inward chloride transporter NKCC1 by furosemide (1mg/100μl) did not reduce electrically evoked pain ratings nor did repetitive GABA stimulation in combination with an inhibited NKCC1 driven chloride replenishment by furosemide. Finally, we generated a sustained period of C-fiber firing by iontophoretically delivering codeine or histamine to induce tonic itch. Neither the intensity nor the duration of histamine or codeine itch was affected by prior injection of furosemide. We conclude that although GABA can evoke calcium transients in a proportion of isolated mouse DRG neurons, it does not induce or modify pain or itch ratings in healthy human skin even when chloride gradients are altered by inhibition of the sodium coupled NKCC1 transporter. [ABSTRACT FROM AUTHOR]

Histamine is a modulatory neurotransmitter, which has received relatively less attention in the central nervous system than other neurotransmitters. The functional role of histamine in the neocortex, the brain region that controls higher‐order cognitive functions such as attention, learning and memory, remains largely unknown. This article focuses on the emerging roles and mechanisms of histamine release in the neocortex. We describe gaps in current knowledge and propose the application of interdisciplinary tools to dissect the detailed multiscale functional logic of histaminergic action in the neocortex ranging from sub‐cellular, cellular, dendritic and synaptic levels to microcircuits and mesoscale effects. [ABSTRACT FROM AUTHOR]

Background: To assess the prevalence of diamine oxidase (DAO) enzyme deficiency caused by single nucleotide polymorphisms (SNPs) of the AOC1 gene in a sample of patients with symptoms of insomnia. Methods: A total of 167 adult patients (>18 years of age) with symptoms of insomnia attended a specialized institute for healthy sleep, in Barcelona (Spain), between May and November 2023, and underwent genotyping analysis of the four most relevant SNP variants, including c.691G>7 (rs2052129), c.47C>T (rs10156191), c.995C>T (rs1049742), and c.1990C>G (rs1049793). Results: Genetic DAO deficiency was present in 138 patients, with a prevalence rate of 82.6% (95% CI 76–88.1%). Difficulties in staying asleep were the most common complaints in 88% of patients followed by trouble falling asleep in 60.5%. More than half of patients suffered from insomnia symptoms every day. Also, 99.4% reported daytime consequences of insomnia, with fatigue (79.6%), mood changes (72.5%), and impaired concentration in 70.1%. When patients were grouped by DAO-score, which reflected the number of heterozygous and homozygous SNPs variants, the group with a DAO-score ≥ 4 vs. 1 showed higher percentages of insomnia-related symptoms, in particular, trouble staying asleep and early morning awakening. These two symptoms were also more common in the presence of the c.1990C>G (rs1049793) variant. Conclusions: This preliminary real-world study presents novel evidence of a potential link between a DAO enzyme deficiency of a genetic origin and clinical symptoms of insomnia, which may suggest the potential benefit of DAO supplementation to improve the quality of sleep in these subjects. The study was registered at ClinicalTrials.gov (NCT06488027). [ABSTRACT FROM AUTHOR]

Background and Aims Methods Results Conclusion The role of histamine in advanced chronic liver disease (ACLD) is poorly understood. We investigated plasma histamine levels across ACLD stages and their prognostic value.We included patients with evidence of ACLD, defined by portal hypertension (hepatic venous pressure gradient [HVPG] ≥6 mmHg) and/or a liver stiffness measurement by transient elastography ≥10 kPa, who underwent HVPG measurement between 2017 and 2020. Acute‐on‐chronic liver failure (ACLF) and/or liver‐related death were defined as composite endpoint.Of 251 patients, 82.5% had clinically significant portal hypertension (median HVPG: 17 mmHg [interquartile range (IQR) 12–21]) and 135 patients (53.8%) were decompensated at baseline.Median plasma histamine was 8.5 nmol/L (IQR: 6.4–11.5), 37.1% of patients showed elevated values (>9.9 nmol/L). Histamine levels did not differ significantly across Child‐Turcotte‐Pugh (CTP) stages nor strata of model for end‐stage liver disease (MELD) or HVPG. Histamine levels correlated with markers of circulatory dysfunction (i.e. sodium, renin and aldosterone).During a median follow‐up of 29.2 months, 68 patients developed ACLF or liver‐related death. In univariate as well as in multivariate analysis (adjusting for age, sex, HVPG as well as either MELD, clinical stage, and serum albumin or CTP and serum sodium), elevated histamine levels remained associated with the composite endpoint. CTP‐based multivariate model adjusted sub‐distribution hazard ratio (asHR): 1.010 (95% CI: 1.004–1.021), p < .001; MELD‐based multivariate model asHR: 1.030 (95% CI: 1.017–1.040), p < .001.High levels of histamine were linked to circulatory dysfunction in ACLD patients and independently associated with increased risks of ACLF or liver‐related death. Further mechanistic studies on the link between histamine signalling and development of hyperdynamic circulation and ACLF are warranted. [ABSTRACT FROM AUTHOR]

Most of the biogenic amines are naturally found in fermented foods as a consequence of amino acid decarboxylation. Their formation is ascribable to microorganisms (starters, contaminants and autochthonous) present in the food matrix. The concentration of these molecules is important for food security reasons, as they are involved in food poisoning illnesses. The most frequent amines found in foods are histamine, putrescine, cadaverine, tyramine, tryptamine, phenylethylamine, spermine and spermidine. One of the most risk-prone foods are cheeses, mostly ripened ones, which could easily accumulate amines due to their peculiar manufacturing process and ripening. Cheeses represent a pivotal food in our diet, providing for nutrients such as amino acids, calcium, vitamins and others; thus, since they are widely consumed, it is important to evaluate the presence of toxic molecules to avoid consumers' poisoning. This review aimed to gather general information on the role of biogenic amines, their formation, the health issues and the microorganisms and processes that produce/reduce them, with a focus on their content in different types of cheese (from soft to hard cheeses) and the biotic and abiotic factors that influence their formation or reduction and concentration. Finally, a multivariate analysis was performed on the biogenic amine content, derived from data available in the literature, to obtain more information about the factors influencing their presence in cheeses. [ABSTRACT FROM AUTHOR]

This study is the first to focus on the preconcentration and determination of histamine (HIS) in food samples using zeolite imidazole frameworks (ZIFs) on a solid-phase microextraction (SPME) platform. ZIF was developed on a polypropylene hollow fiber (PPHF) substrate (ZIF@PPHF) and characterized. The extraction performance was optimized by adjusting several parameters, including pH, contact time for adsorption, and desorption conditions. Under the optimized conditions, a wide linear dynamic range (0.05–250 mg/L) with high R2 values (0.9989), low limit of detection (0.019 mg/L), and low limit of quantification (0.050 mg/L) were determined as analytical figures of merit. Additionally, a reusability study confirmed that ZIF@PPHF preconcentrated 83% of the HIS up to the fourth cycle. The developed method was used to preconcentrate HIS in fish and cheese samples. The spiked real samples confirmed the validity and accuracy of this method. The percentage mean recoveries ± relative standard deviation (% RSD, n = 3) at the concentration levels of 5, 10, and 50 mg/L of HIS and the sample amount of 5 g for intra- and inter days ranged from 97 ± 1.10 to 102.80 ± 0.90 and from 96.40 ± 1.82 to 103.40 ± 0.79, respectively. The results suggest that the analytical method validation parameters were acceptable, indicating the repeatability and sensitivity of the method. [ABSTRACT FROM AUTHOR]

The effect of using camel milk on the physiochemical, microbiological and sensory properties, and free amino acid and biogenic amine contents of processed Domiati cheese was investigated during pickling (90 days) at 4°C. The results revealed a decrease in biogenic amines and an increase in free amino acids in cheese made from camel milk compared to cheese made from buffalo milk. Histamine and tryptamine were the most predominant amines in all the treatments (13 and 12 mg/kg), respectively. All samples had lower than the allowable level of biogenic amines, according to the Food and Drug Administration (10 mg/100 g). [ABSTRACT FROM AUTHOR]

Summary: Impacts of aqueous and ethanolic extracts of garlic were investigated in suppressing bacterial growth and biogenic amine (BA) formation by selected foodborne pathogens (Candida albicans, Salmonella paratyphi A, Escherichia coli and Staphylococcus aureus) and fish spoilage bacteria (Enterococcus faecalis, Photobacterium damselae and Pseudomonas luteola). The spread‐plate method was used to monitor bacterial growth in histidine decarboxylase broth (HDB), whereas the rapid high‐performance liquid chromatographic (HPLC) method was used for BA analysis. Bacterial growth and their ammonia and BA production were monitored using HDB. The results showed that bacterial growth on HDB was in the range from 9.13, for P. luteola, to 9.54 log CFU (colony‐forming units) mL−1, for S. aureus and C. albicans. The presence of garlic extracts in HDB resulted considerably in lowering bacterial growth and BA formation (P < 0.05). The highest inhibitory activities of ethanolic and water garlic extracts were obtained for Gram‐positive S. aureus with 1.4 and 1.5 logarithmic reduction on bacterial growth, followed by Gram‐negative Salmonella Paratyphi A and E. coli. Application of garlic extracts, mainly ethanolic ones, showed a significant inhibitory effect on bacterial ammonia production, with 4‐100‐fold lower ammonia accumulation (P < 0.05). Bacteria produced all tested BAs, mainly dopamine, agmatine and tryptamine. The highest levels of histamine and tyramine (61.99 and 36.45 mg L−1) were produced by S. aureus. In the presence of aqueous or ethanolic garlic extracts, putrescine production by E. faecalis was around 110‐fold lower than that of the control group. Results revealed that both garlic extracts are potent antimicrobials that can control the growth of foodborne pathogens and their harmful BA formation. [ABSTRACT FROM AUTHOR]

The presence of biogenic amines (BAs) in seafood can pose a health risk to consumers, as they have been linked to adverse reactions such as histamine poisoning. Although the only biogenic amine for which maximum limits have been set is histamine, it is also important to regulate the presence of other amines associated with certain adverse effects. In this study, the official method for determining histamine was slightly modified and adapted for a UHPLC-PDA system and applied to analyze raw and preserved mackerel fillet samples. The evolution of biogenic amines during the storage period under refrigerated conditions revealed that, within two days, the limit for the content of histidine of 100 mg/kg was exceeded in raw fillets, while the histidine content in preserved mackerel (in oil and marinated) remained more stable. The thawing phase, whether in the fridge or at room temperature, did not significantly affect the BA content. Additionally, three different cooking methods (steaming, oven-baking, and boiling) significantly decrease the levels of BAs in highly contaminated raw mackerel fillets. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease resulting in decreased quality of life. Histamine and specifically the H4 receptor play a key role in the inflammatory process in AD and serve as targets for novel therapeutic approaches. Objective: In the present study we aimed to elucidate the immunopathological mechanisms with which the H4 receptor impacts TH2 cells and contributes to AD pathophysiology. Methods: Total CD4+ T cells obtained from healthy or AD individuals and in vitro differentiated TH2 cells were cultured under different conditions and the mRNA expression or protein production of target molecules were determined using quantitative real‐time PCR and ELISA. Results: H4 receptor mRNA expression was upregulated concentration dependent upon IL‐4 stimulation in in vitro differentiated TH2 cells progressively during the differentiation. Transcriptomic analysis of in vitro differentiated TH2 versus TH1 cells revealed that the H4 receptor among other genes represents one of the highly upregulated genes in TH2 cells. Most importantly, increased amounts of IL‐5 and IL‐13 mRNA expression were detected in in vitro differentiated TH2 cells as well as protein secretion in the presence of histamine or of the H4 receptor‐selective‐agonist when compared to the untreated control. Conclusion: We show for the first time an H4 receptor dependent upregulation of the pro‐inflammatory cytokines IL‐5 and IL‐13 in human TH2 cells by histamine. This suggests that the blockade of the H4 receptor may lead to downregulation of these cytokines and amelioration of AD symptoms as reported in first clinical studies. [ABSTRACT FROM AUTHOR]

Intestinal mucosal immune cells, notably mast cells, are pivotal in ulcerative colitis (UC) pathophysiology. Its activation elevates tissue concentrations of histamine. Inhibiting colonic histamine release could be an effective therapeutic strategy for treating UC. Experimental model like 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats mimic human IBD, aiding treatment investigations. Drug repurposing is a promising strategy to explore new indications for established drugs. Desloratadine (DES) is second-generation antihistamine utilized for managing allergies by blocking histamine action in the body. It also has reported anti-inflammatory and antioxidant actions. DES was investigated for its repurposing potential in UC by preclinical screening in TNBS-induced colitis in Wistar rats. Therapeutic efficacy of DES was evaluated both individually and in combination with standard drug 5-aminosalicylicacid (5-ASA). Rats were orally administered DES (10 mg/kg), 5-ASA (25 mg/kg), and DES + 5-ASA (5 mg + 12.15 mg) following the induction of colitis. Parameters including disease activity score rate (DASR), colon/body weight ratio (CBWR), colon length, diameter, pH, histological injury, and scoring were evaluated. Inflammatory biomarkers such as IL-1β, TNF-α, along with reduced glutathione (GSH), and malondialdehyde (MDA) were assessed. Significant protective effects of DES, especially in combination with 5-ASA, against TNBS-induced inflammation were observed as evidenced by reduced DASR, CBWR, and improved colon morphology. Drugs significantly lowered plasma and colon histamine and, cytokines levels. GSH restoration, and decreased MDA content were also observed. DES and DES + 5-ASA demonstrated potential in alleviating colonic inflammation associated with TNBS-induced colitis in rats. The effect can be attributed to its antihistamine, anticytokine, and antioxidative properties. [ABSTRACT FROM AUTHOR]

Introduction: Mast cells are known for their involvement in allergic reactions but also in inflammatory reactions via secretion of numerous pro-inflammatory chemokines, cytokines, and enzymes. Drug development has focused on antiproliferative therapy for systemic mastocytosis and not on inhibitors of mast cell activation. The only drug available as a "mast cell blocker" is disodium cromoglycate (cromolyn), but it is poorly absorbed after oral administration, is a weak inhibitor of histamine release from human mast cells, and it develops rapid anaphylaxis. Instead, certain natural flavonoids, especially luteolin, can inhibit mast cell activation. Methods: Here, we compared pretreatment (0–120 min) with equimolar concentration (effective dose for 50% inhibition = 100 mm for inhibition of histamine release by cromolyn) of cromolyn and luteolin on release of mediators from the cultured human LADR mast cell line stimulated either by immunoglobulin E (IgE) and anti-IgE or with IL-33. Results: We show that luteolin is significantly more potent than cromolyn inhibiting release of histamine, tryptase, metalloproteinase-9, and vascular endothelial growth factor. Moreover, while luteolin also significantly inhibited release of IL-1β, IL-6, and IL-8 (CXCL8) and TNF, cromolyn had no effect. Conclusion: These findings support the use of luteolin, especially in liposomal form to increase oral absorption, may be a useful alternative to cromolyn. [ABSTRACT FROM AUTHOR]

The endothelial glycocalyx (EG), covering the luminal side of endothelial cells, regulates vascular permeability and senses wall shear stress. In sepsis, EG undergoes degradation leading to increased permeability and edema formation. We hypothesized that restoring EG integrity using liposomal nanocarriers of preassembled glycocalyx (LNPG) will restore normal venular permeability in lipopolysaccharide (LPS)-induced sepsis model of mice. To test this hypothesis, we designed a unique perfusion microchamber in which the permeability of isolated venules could be assessed by measuring the concentration of Evans blue dye (EBD) in microliter samples of extravascular solution (ES). Histamine-induced time- and dose-dependent increases in EBD in the ES could be measured, confirming the sensitivity of the microchamber system. Notably, the histamine-induced increase in permeability was significantly attenuated by histamine receptor (H1) antagonist, triprolidine hydrochloride. Subsequently, mice were treated with LPS or LPS + LNPG. When compared with control mice, venules from LPS-treated mice showed a significant increased permeability, which was significantly reduced by LNPG administration. Moreover, in the presence of wall shear stress, intraluminal administration of LNPG significantly reduced the permeability in isolated venules from LPS-treated mice. We have found no sex differences. In conclusion, our newly developed microchamber system allows us to quantitatively measure the permeability of isolated venules. LPS-induced sepsis increases permeability of mesenteric venules that is attenuated by in vivo LNPG administration, which also reestablished endothelial responses to shear stress. Thus, LNPG presents a promising therapeutic potential for restoring EG function and thereby mitigating vasogenic edema due to increased permeability in sepsis. NEW & NOTEWORTHY: In sepsis, the degradation of the endothelial glycocalyx leads to increased venular permeability. In this study, we developed a potentially new therapeutic approach by in vivo administration of liposomal nanocarriers of preassembled glycocalyx to mice, which restored venular sensitivity to wall shear stress and permeability in lipopolysaccharide-induced sepsis, likely by restoring the integrity of the endothelial glycocalyx. Using a new microchamber system, the permeability of Evans blue dye could be quantitatively determined. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignancy in women, and despite the development of new treatment methods and the decreasing mortality rate in recent years, one of the clinical problems in breast cancer treatment is chronic inflammation in the tumor microenvironment. Histamine, an inflammatory mediator, is produced by tumor cells and can induce chronic inflammation and the growth of some tumors by recruiting inflammatory cells. It can also affect tumor physiopathology, antitumor treatment efficiency, and patient survival. Antihistamines, as histamine receptor antagonists, play a role in modulating the effects of these receptors in tumor cells and can affect some treatment methods for breast cancer therapy; in this review, we investigate the role of histamine, its receptors, and antihistamines in breast cancer pathology and treatment methods. [ABSTRACT FROM AUTHOR]

Globally, hepatitis C virus (HCV) and coronavirus disease 2019 (COVID‐19) are the most common causes of death due to the lack of early predictive and diagnostic tools. Therefore, research for a new biomarker is crucial. Inflammatory biomarkers are critical central players in the pathogenesis of viral infections. IL‐18, produced by macrophages in early viral infections, triggers inflammatory biomarkers and interferon production, crucial for viral host defense. Finding out IL‐18 function can help understand COVID‐19 pathophysiology and predict disease prognosis. Histamine and its receptors regulate allergic lung responses, with H1 receptor inhibition potentially reducing inflammation in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. angiotensin‐converting enzyme 2 (ACE‐2) receptors on cholangiocytes suggest liver involvement in SARS‐CoV‐2 infection. The current study presents the potential impact of circulating acetylcholine, histamine, IL‐18, and interferon‐Alpha as diagnostic tools in HCV, COVID‐19, and dual HCV‐COVID‐19 pathogenesis. The current study was a prospective cross‐section conducted on 188 participants classified into the following four groups: Group 1 COVID‐19 (n = 47), Group 2 HCV (n = 47), and Group 3 HCV‐COVID‐19 patients (n = 47), besides the healthy control Group 4 (n = 47). The levels of acetylcholine, histamine, IL‐18, and interferon‐alpha were assayed using the ELISA method. Liver and kidney functions within all groups showed a marked alteration compared to the healthy control group. Our statistical analysis found that individuals with dual infection with HCV‐COVID‐19 had high ferritin levels compared to other biomarkers while those with COVID‐19 infection had high levels of D‐Dimer. The histamine, acetylcholine, and IL‐18 biomarkers in both COVID‐19 and dual HCV‐COVID‐19 groups have shown discriminatory power, making them potential diagnostic tests for infection. These three biomarkers showed satisfactory performance in identifying HCV infection. The IFN‐Alpha test performed well in the HCV‐COVID‐19 group and was fair in the COVID‐19 group, but it had little discriminative value in the HCV group. Moreover, our findings highlighted the pivotal role of acetylcholine, histamine, IL‐18, and interferon‐Alpha in HCV, COVID‐19, and dual HCV‐COVID‐19 infection. Circulating levels of acetylcholine, histamine, IL‐18, and interferon‐Alpha can be potential early indicators for HCV, COVID‐19, and dual HCV‐COVID‐19 infection. We acknowledge that further large multicenter experimental studies are needed to further investigate the role biomarkers play in influencing the likelihood of infection to confirm and extend our observations and to better understand and ultimately prevent or treat these diseases. [ABSTRACT FROM AUTHOR]

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Background/Objectives: Quantification of diamine oxidase (DAO) concentrations in serum has been proposed as an adjunctive diagnostic modality for the evaluation of histamine intolerance (HIT). Limited empirical data exist concerning the influence of dietary patterns on DAO levels. Subjects/Methods: In the context of a prospective study employing a crossover design, 18 individuals diagnosed with HIT were randomized to initiate either a low histamine diet (LHD) or a conventional mixed diet (MXD). Serum DAO concentrations were measured at the commencement of the study and following each dietary phase. A control group underwent analogous DAO assessments without imposition of dietary constraints. Results: During the time when a diet restricted in histamine was implemented, noticeable differences in changes in DAO levels did not become apparent when compared to the changes observed during the mixed (MXD) phase. Specifically, among the group, 10 of the 18 patients exhibited elevated DAO values subsequent to the LHD regimen, while the remaining eight displayed either reduced or unchanging DAO levels. The prevalence of elevated DAO levels in the LHD group did not differ significantly from that observed in the control group during the MXD phase. Additionally, during the LHD phase, patients reported a significant reduction in gastrointestinal and cutaneous symptoms. Conclusions: This prospective investigation underscores the enduring utility of a histamine-restricted diet, coupled with structured dietary reintroduction, as an efficacious diagnostic approach for individuals presenting with suspected food-related histamine hypersensitivity. Notably, the measurement of DAO levels appears to furnish only a limited capacity to discern dietary-induced fluctuations. Notwithstanding, the dynamics of DAO alteration do not appear to exhibit a discernible association with specific dietary patterns, a finding consistent across both patient and control groups. [ABSTRACT FROM AUTHOR]

Summary Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition associated with altered bowel habits and recurrent abdominal pain, often triggered by food intake. Current treatments focus on improving stool pattern, but effective treatments for pain in IBS are still lacking due to our limited understanding of pathophysiological mechanisms. Visceral hypersensitivity (VHS), or abnormal visceral pain perception, underlies abdominal pain development in IBS, and mast cell activation has been shown to play an important role in the development of VHS. Our work recently revealed that abdominal pain in response to food intake is induced by the sensitization of colonic pain‐sensing neurons by histamine produced by activated mast cells following a local IgE response to food. In this review, we summarize the current knowledge on abdominal pain and VHS pathophysiology in IBS, we outline the work leading to the discovery of the role of histamine in abdominal pain, and we introduce antihistamines as a novel treatment option to manage chronic abdominal pain in patients with IBS. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is characterized by a long prodromal period, during which patients often have sleep disturbances. The histaminergic system and circadian rhythms play an important role in the regulation of the sleep–wake cycle. Changes in the functioning of these systems may be involved in the pathogenesis of early stages of PD and may be age-dependent. Here, we have analyzed changes in the expression of genes associated with the regulation of the sleep–wake cycle (Hnmt, Hrh1, Hrh3, Per1, Per2, and Chrm3) in the substantia nigra (SN) and striatum of normal male mice of different ages, as well as in young and adult male mice with an MPTP-induced model of the early symptomatic stage (ESS) of PD. Age-dependent expression analysis in normal mouse brain tissue revealed changes in Hrh3, Per1, Per2, and Chrm3 genes in adult mice relative to young mice. When gene expression was examined in mice with the MPTP-induced model of the ESS of PD, changes in the expression of all studied genes were found only in the SN of adult mice with the ESS model of PD. These data suggest that age is a significant factor influencing changes in the expression of genes associated with sleep–wake cycle regulation in the development of PD. [ABSTRACT FROM AUTHOR]

Introduction: We previously showed enteric nerve activation after application of colonic mucosal biopsy supernatants from patients with irritable bowel syndrome (IBS). The question remains whether this is a region-specific or a generalized sensitization. We tested the nerve-activating properties of supernatants from large and small intestinal regions of IBS patients with diarrhea (IBS-D) in comparison to those from mastocytosis patients with diarrhea (MC-D) or non-IBS/non-MC patients with GI-complaints. MC-D patients were included to test samples from patients with an established, severe mast cell disorder, because mast cells are suggested to play a role in IBS. Methods: Voltage-sensitive dye imaging was used to record the effects of mucosal biopsy supernatants from IBS-D, MC-D, and non-IBS/non-MC on guinea pig submucous neurons. Mast cell density and histamine concentrations were measured in all samples. Results: The median neuroindex (spike frequency × % responding neurons in Hz × %) was significantly (all p < 0.001) increased for IBS-D (duodenum and colon, proximal and distal each, 49.3; 50.5; 63.7; 71.9, respectively) compared to non-IBS/non-MC (duodenum and colon, proximal and distal each, 8.7; 4.9; 6.9; 5.4, respectively) or MC-D supernatants (duodenum and colon, proximal and distal each, 9.4; 11.9; 0.0; 7.9, respectively). Nerve activation by MC-D and non-IBS/non-MC supernatants was comparable (p>0.05). Mast cell density or histamine concentrations were not different between IBS-D, MC-D, and non-IBS/non-MC samples. Discussion: Nerve activation by biopsy supernatants is an IBS hallmark that occurs throughout the gut, unrelated to mast cell density or histamine concentration. At least as important is our finding that GI complaints per se were not associated with biopsy supernatant-induced nerve activation, which further stresses the relevance of altered nerve behavior in IBS. [ABSTRACT FROM AUTHOR]

Accumulating evidence shows that inflammation is essential for embryo implantation and decidualization. Histamine, a proinflammatory factor that is present in almost all mammalian tissues, is synthesized through decarboxylating histidine by histidine decarboxylase (HDC). Although histamine is known to be essential for decidualization, the underlying mechanism remains undefined. In the present study, histamine had no obvious direct effects on in vitro decidualization in mice. However, the obvious differences in HDC protein levels between day 4 of pregnancy and day 4 of pseudopregnancy, as well as between delayed and activated implantation, suggested that the blastocyst may be involved in regulating HDC expression. Furthermore, blastocyst‐derived tumor necrosis factor α (TNFα) significantly increased HDC levels in the luminal epithelium. Histamine increased the levels of amphiregulin (AREG) and disintegrin and metalloproteinase domain‐containing protein 17 (ADAM17) proteins, which was abrogated by treatment with famotidine, a specific histamine type 2 receptor (H2R) inhibitor, or by TPAI‐1 (a specific inhibitor of ADAM17). Intraluminal injection of urocanic acid (HDC inhibitor) on day 4 of pregnancy significantly reduced the number of implantation sites on day 5 of pregnancy. TNFα‐stimulated increases in HDC, AREG and ADAM17 protein levels was abrogated by urocanic acid, a specific inhibitor of HDC. Additionally, AREG treatment significantly promoted in vitro decidualization. Collectively, our data suggests that blastocyst‐derived TNFα induces luminal epithelial histamine secretion, and histamine increases mouse decidualization through ADAM17‐mediated AREG release. [ABSTRACT FROM AUTHOR]

Biogenic amines are signaling molecules with multiple roles in the central nervous system and in peripheral organs, including the gonads. A series of studies indicated that these molecules, their biosynthetic enzymes and their receptors are present in the testis and that they are involved in the regulation of male reproductive physiology and/or pathology. This mini-review aims to summarize the current knowledge in this field and to pinpoint existing research gaps. We suggest that the widespread clinical use of pharmacological agonists/antagonists of these signaling molecules, calls for new investigations in this area. They are necessary to evaluate the relevance of biogenic amines for human male fertility and infertility, as well as the potential value of at least one of them as an anti-aging compound in the testis. [ABSTRACT FROM AUTHOR]

Cheese is a food in which toxic concentrations of biogenic amines (BA) may be reached, mainly as a consequence of the decarboxylation of determined amino acids by certain lactic acid bacteria (LAB). To maintain the food safety of cheese, environmentally friendly strategies are needed that specifically prevent the growth of BA-producing LAB and the accumulation of BA. The bacteriocins produced by LAB are natural compounds with great potential as food biopreservatives. This work examines the antimicrobial potential of 7 bacteriocin-containing, cell-free supernatants (CFS: coagulin A-CFS, enterocin A-CFS, enterocin P-CFS, lacticin 481-CFS, nisin A-CFS, nisin Z-CFS and plantaricin A-CFS) produced by LAB against 48 strains of the LAB species largely responsible for the accumulation of the most important BA in cheese, that is, histamine, tyramine, and putrescine. Susceptibility to the different CFS was strain-dependent. The histamine-producing species with the broadest sensitivity spectrum were Lentilactobacillus parabuchneri (the species mainly responsible for the accumulation of histamine in cheese) and Pediococcus parvulus. The tyramine-producing species with the broadest sensitivity spectrum was Enterococcus faecium , and Enterococcus faecalis and Enterococcus hirae were among the most sensitive putrescine producers. Nisin A-CFS was active against 31 of the 48 BA-producing strains (the broadest antimicrobial spectrum recorded). Moreover, commercial nisin A prevented biofilm formation by 67% of the BA-producing, biofilm-forming LAB strains. These findings underscore the potential of bacteriocins in the control of BA-producing LAB and support the use of nisin A as a food-grade biopreservative for keeping BA-producing LAB in check and reducing BA accumulation in cheese. [ABSTRACT FROM AUTHOR]

Key points The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole‐cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)‐Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC‐δ‐ and SOM‐positive CeL neurons. The histamine‐induced effect is mediated by H3 receptors expressed on VGLUT1‐/VGLUT2‐positive presynaptic terminals in CeL. Furthermore, optoactivation of histaminergic afferent terminals from the hypothalamic tuberomammillary nucleus (TMN) also significantly suppresses glutamatergic transmissions in CeL via H3 receptors. Histamine neither modulates inhibitory synaptic transmission by presynaptic H3 receptors nor directly excites CeL neurons by postsynaptic H1, H2 or H4 receptors. These results suggest that histaminergic afferent inputs and presynaptic H3 heteroreceptors may hold a critical position in balancing excitatory and inhibitory synaptic transmissions in CeL by selective modulation of glutamatergic drive, which may not only account for the pathophysiology of psychiatric disorders but also provide potential psychotherapeutic targets. Histamine selectively suppresses the excitatory, rather than inhibitory, synaptic transmissions on both PKC‐δ‐ and SOM‐positive neurons in the centrolateral amygdala (CeL). H3 receptors expressed on VGLUT1‐ or VGLUT2‐positive afferent terminals mediate the suppression of histamine on glutamatergic synaptic transmission in CeL. Optogenetic activation of hypothalamic tuberomammillary nucleus (TMN)–CeL histaminergic projections inhibits glutamatergic transmission in CeL via H3 receptors. [ABSTRACT FROM AUTHOR]

The application of biosensors in complex realworld samples is often complicated due to the combined effects and interferences of various compounds on the biosensor signal. However, thorough modelling and chemometric methods allow us to evaluate the impact of different analytes and calibrate these biosensors for the multiplexed analyses of the targeted compounds. A typical multianalyte mixture includes biogenic amines, produced during the putrefaction of proteins. Meanwhile, the detection of particular biogenic amines is a valuable tool for assessing the freshness and quality of a wide variety of proteincontaining foods. In the current study, we analysed the signal of biosensors for the simultaneous detection of four major biogenic amines (cadaverine, putrescine, histamine, and spermidine) and proposed two different approaches for their multivariate calibration. The evaluation of the proposed models and the calculation of their characteristic coefficients were based on experimental data from over three hundred different mixtures with randomly varying substrate concentrations. [ABSTRACT FROM AUTHOR]

A 10‐year‐old, neutered male, Golden Retriever dog presented for surgical correction of a descemetocele. Acepromazine (0.02 mg/kg) and methadone (0.5 mg/kg) were administered intramuscularly for sedation, propofol (2 mg/kg) and midazolam (0.2 mg/kg) were administered intravenously for anaesthetic induction and isoflurane in oxygen was utilised for anaesthetic maintenance. Rocuronium (0.5 mg/kg), a neuromuscular blocking agent, was administered intravenously to facilitate central positioning of the eye for surgery. Within 10 min of rocuronium administration, the dog became tachycardic and hypotensive. Hemodynamic aberrations did not resolve with initial interventions but were successfully mitigated with the administration of diphenhydramine (0.8 mg/kg) intravenously. The dog remained stable throughout the remainder of the procedure and experienced a smooth and uneventful recovery. While it is difficult to confirm that the hemodynamic changes observed in this clinical case resulted solely from administration of rocuronium, the observance of the cardiovascular changes, timing of events and response to therapy suggest that rocuronium elicited a histamine response that was successfully treated with diphenhydramine. [ABSTRACT FROM AUTHOR]

Allergic rhinitis is a common disorder that is strongly linked to asthma and conjunctivitis. It is usually a long-standing condition that often goes undetected in the primary care setting Allergic Rhinitis (AR) is a very common, under recognised problem in the UK with symptoms significantly impacting on quality of life, work and school performance, social life and is a risk factor for developing asthma. Treatment options for AR include allergen avoidance, antihistamines and intra-nasal pharmacological therapies. [ABSTRACT FROM AUTHOR]

This study investigated the safety and functionality of traditional African sourdough flatbread (kisra), based on the content of biogenic amines (BAs) and antioxidant compounds and their improvement using lactic acid bacteria (LAB) species. The primary BAs detected in naturally fermented kisra were tyramine, histamine, putrescine, and cadaverine, with putrescine being the most abundant after baking. In vitro BA production of microorganisms isolated from kisra sourdough revealed that the Enterococcus genus contributed to tyramine accumulation, whereas presumptive yeasts may contribute to putrescine and cadaverine accumulation. The use of LAB species, including Lactiplantibacillus plantarum, Limosilactobacillus fermentum, Levilactobacillus brevis, and Weissella cibaria, significantly reduced putrescine content to less than about 23% of that of naturally fermented kisra, and eliminated tyramine, histamine, and cadaverine formation. Meanwhile, DPPH scavenging activity, total polyphenolic content, and tannin content in naturally fermented kisra were 85.16%, 1386.50 µg/g, and 33.16 µg/g, respectively. The use of LAB species did not affect the DPPH scavenging activity or tannin content but significantly increased the total phenolic content by up to 20% compared to naturally fermented kisra. Therefore, fermentation with LAB starter cultures might be a promising approach to improve the safety related to BAs as well as the functionality of kisra bread. [ABSTRACT FROM AUTHOR]

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Background and Objectives: An oral lichen planus (OLP) chronic lesion refers to a group of oral potentially malignant disorders (OPMDs) that still lack a proper understanding from the point of view of relevant biomarkers for diagnostics and prognosis. The aim of the study was to assess the salivary histamine levels in patients with oral lichen planus lesions. Materials and Methods: The study included a group of 76 patients with oral lichen planus. General diseases and medication taken, smoking habits, severity of pain assessed using a visual analogue scale (VAS), oral hygiene status, and duration of OLP were evaluated. ELISA diagnostics for histamines in saliva levels were assessed. Results: The histamine levels in the OLP group were higher (0.468) in comparison with the control group (0.056), without a statistically significant value p = 0.090 (Mann–Whitney U Test). The median age of 76 OLP patients was 63 years (min 22.0–max. 81), with the biological sex being 80.3% females and 15 19.7% males. The average duration of OLP lesion presence was 29.4 months (SD 37.1) and the median value was 14.5 months. The median of the VAS was 3.0. OLP assessment in accordance with the Malhotra methodology showed the highest frequency—30.3% for only two of the point areas involved and 17.1% for three points. Clinical assessment of the different OLP grades, severity, and oral site involvement and the VAS in correlation with histamine salivary levels showed a lack of statistical significance in the investigated population. Conclusions: Undertaking further research could provide further possibilities for searching for general factors in OLP development. [ABSTRACT FROM AUTHOR]

Histamine is a biogenic amine that regulates multiple physiological functions in diverse organisms, specifically playing a central role in the mammalian immune response. The common bed bug, Cimex lectularius L. (Hemiptera: Cimicidae), excretes histamine in large amounts in its feces as a component of its aggregation pheromone, which contaminates homes. The potential health risks associated with the presence of indoor histamine are unclear, but to predict future exposure risks, it is critical that we understand if other arthropods excrete histamine in any discernible phylogenetic pattern. In the present study, we evaluated histamine excretion by various arthropods; specifically those commonly found in large numbers indoors, other hematophagous species, and other species in the order Hemiptera. To evaluate arthropods for histamine excretion, rearing containers for each arthropod were swabbed and/or the harborage substrates were collected. Samples were then analyzed for the presence of histamine using gas chromatography-mass spectrometry. For those arthropods where histamine was present above the method detection limit, total histamine excretion was quantified over a period of 2 wk. Our results indicate that histamine excretion is limited to hematophagous hemipterans (bed bugs, bat bugs, tropical bed bugs, and kissing bugs), suggesting that indoor histamine contamination in the United States can be primarily linked to bed bugs.

Aims: This study investigated histamine intake and its associations with clinical and biochemical findings in patients with Behçet syndrome. Methods: Patients with Behçet syndrome were prospectively enrolled using a cross-sectional, multicenter, and online survey design. Sociodemographic parameters, including age, gender, smoking and alcohol intake, nutritional counseling history, anthropometric measurements, clinical characteristics, and biochemical results, were obtained using an online questionnaire. Dietary histamine intake was determined using a food frequency questionnaire. Results: The study included 66 patients (mean age: 37.5±11.3 years, women: 53%. Food consumption was reported to trigger oral aphthae in 81% of the individuals, and the most frequently reported triggers were eggplant (37.5%), tomatoes (37.5%), and citrus fruits (34.3%). There was a significant positive correlation between dietary histamine intake and white blood cell counts (r=0.650; p=0.050). There were no significant differences in the clinical characteristics, including oral aphthae, genital ulcers, uveitis, dermatologic lesions, gastrointestinal system involvement, joint involvement, and vascular involvement between patients with low and high dietary histamine intake. A positive correlation was found between dietary histamine intake and the frequency of attacks (r=0.324; p=0.008). Conclusions: This study showed that increased dietary histamine intake was associated with an increased frequency of attacks in patients with Behçet syndrome. Oral aphthae are associated with certain foods, such as eggplant, tomatoes, and citrus fruit.

ABSTRACT: Cheese is a food in which toxic concentrations of biogenic amines (BA) may be reached, mainly as a consequence of the decarboxylation of determined amino acids by certain lactic acid bacteria (LAB). To maintain the food safety of cheese, environmentally friendly strategies are needed that specifically prevent the growth of BA-producing LAB and the accumulation of BA. The bacteriocins produced by LAB are natural compounds with great potential as food biopreservatives. This work examines the antimicrobial potential of 7 bacteriocin-containing, cell-free supernatants (CFS: coagulin A-CFS, enterocin A-CFS, enterocin P-CFS, lacticin 481-CFS, nisin A-CFS, nisin Z-CFS and plantaricin A-CFS) produced by LAB against 48 strains of the LAB species largely responsible for the accumulation of the most important BA in cheese, that is, histamine, tyramine, and putrescine. Susceptibility to the different CFS was strain-dependent. The histamine-producing species with the broadest sensitivity spectrum were Lentilactobacillus parabuchneri (the species mainly responsible for the accumulation of histamine in cheese) and Pediococcus parvulus. The tyramine-producing species with the broadest sensitivity spectrum was Enterococcus faecium, and Enterococcus faecalis and Enterococcus hirae were among the most sensitive putrescine producers. Nisin A-CFS was active against 31 of the 48 BA-producing strains (the broadest antimicrobial spectrum recorded). Moreover, commercial nisin A prevented biofilm formation by 67% of the BA-producing, biofilm-forming LAB strains. These findings underscore the potential of bacteriocins in the control of BA-producing LAB and support the use of nisin A as a food-grade biopreservative for keeping BA-producing LAB in check and reducing BA accumulation in cheese.

Human heroin addicts and mice administered morphine for a 2 week period show a greatly increased number of hypothalamic hypocretin (Hcrt or orexin) producing neurons with a concomitant reduction in Hcrt cell size. Male rats addicted to cocaine similarly show an increased number of detectable Hcrt neurons. These findings led us to hypothesize that humans with alcohol use disorder (AUD) would show similar changes. We now report that humans with AUD have a decreased number and size of detectable Hcrt neurons. In addition, the intermingled melanin concentrating hormone (MCH) neurons are reduced in size. We saw no change in the size and number of tuberomammillary histamine neurons in AUD. Within the Hcrt/MCH neuronal field we found that microglia cell size was increased in AUD brains. In contrast, male rats with 2 week alcohol exposure, sufficient to elicit withdrawal symptoms, show no change in the number or size of Hcrt, MCH and histamine neurons, and no change in the size of microglia. The present study indicates major differences between the response of Hcrt neurons to opioids and that to alcohol in human subjects with a history of substance abuse.